MurD enzymes from different bacteria: Evaluation of inhibitors

作者：Barreteau Helene; Sosic Izidor; Turk Samo; Humljan Jan; Tomasic Tihomir; Zidar Nace; Herve Mireille; Boniface Audrey; Peterlin Masic Lucija; Kikelj Danijel; Mengin Lecreulx Dominique; Gobec Stanislav; Blanot Didier^*

来源：Biochemical Pharmacology, 2012, 84(5): 625-632.

DOI：10.1016/j.bcp.2012.06.006

• D-Glutamic acid-adding enzymes
• MurD ligase active sites
• MurD ligase inhibitors
• Pathogenic bacteria
• Peptidoglycan biosynthesis

D-Glutamic acid-adding enzyme (MurD ligase) catalyses the addition of D-glutamic acid to UDP-N-acetylmuramoyl-L-alanine, an essential cytoplasmic step in the pathway for bacterial cell-wall peptidoglycan synthesis. As such, it represents an important antibacterial drug-discovery target enzyme. Recently, several series of compounds have been synthesised and found to inhibit MurD from Escherichia coli, the best one having an IC50 value of 8 mu M. In the present work, we have tested 20 of these compounds against the MurD enzymes from Staphylococcus aureus, Streptococcus pneumoniae, Borrelia burgdorferi and Mycobacterium tuberculosis. Most of the E. coli MurD inhibitors appeared less efficient against the four other orthologues. This divergent result can be explained by the differences in amino acid sequences and topologies of the active sites of the MurD ligases studied.

• 出版日期2012-9-1